Variant 18-3534226-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004746.4(DLGAP1):c.2447G>A(p.Arg816Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0224 in 1,614,058 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.016 ( 34 hom., cov: 32)

Exomes 𝑓: 0.023 ( 448 hom. )

Consequence

DLGAP1
NM_004746.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004804611).

BP6

Variant 18-3534226-C-T is Benign according to our data. Variant chr18-3534226-C-T is described in ClinVar as [Benign]. Clinvar id is 3037438.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2493/152292) while in subpopulation NFE AF= 0.0283 (1927/68026). AF 95% confidence interval is 0.0273. There are 34 homozygotes in gnomad4. There are 1112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2493 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4 link	c.2447G>A	p.Arg816Gln	missense_variant	10/13	ENST00000315677.8	NP_004737.2	O14490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8 link	c.2447G>A	p.Arg816Gln	missense_variant	10/13	5	NM_004746.4	ENSP00000316377.3		O14490-1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2494

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.0155

AC:

3898

AN:

250866

Hom.:

AF XY:

0.0155

AC XY:

2102

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.00752

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.0119

Gnomad NFE exome

AF:

0.0264

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0230

AC:

33659

AN:

1461766

Hom.:

448

Cov.:

AF XY:

0.0225

AC XY:

16326

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.00816

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00404

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.0275

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0164

AC:

2493

AN:

152292

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1112

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00503

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0110

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0237

Hom.:

Bravo

AF:

0.0157

TwinsUK

AF:

0.0278

AC:

103

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0255

AC:

219

ExAC

AF:

0.0160

AC:

1942

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0228

EpiControl

AF:

0.0234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLGAP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

.;.;.;.;T;T;.;.;.;.;.

Eigen

Benign

-0.063

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

D;D;.;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0048

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

.;.;.;.;.;N;.;.;.;.;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.69

N;N;N;N;.;N;N;N;.;N;.

REVEL

Benign

0.068

Sift

Benign

0.28

T;T;T;T;.;T;T;T;.;T;.

Sift4G

Benign

0.59

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.014

B;.;.;.;.;B;.;.;.;B;.

Vest4

0.16

MPC

1.0

ClinPred

0.014

GERP RS

5.9

Varity_R

0.095

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over